Anti-tuberculosis (TB) drugs cause changes to gut microbiota and increase susceptibility to Mycobacterium tuberculosis (Mtb) -- a major reason why current treatments are ineffective in preventing reinfections, say researchers.
The study showed that chronic use of antibiotics controls TB infection but also leads to disruption of gut microbiota. This, in turn, leads to the dysregulation of the immune system, causing reinfection.
"Anti-TB therapies have been incredibly efficient in controlling the TB epidemic by decreasing morbidity and mortality associated with Mtb," said Irah King from the McGill University in Canada.
"This study provides a basis for novel therapeutic strategies exploiting the gut-lung axis in Mtb infection," King added.
For the study, the researchers treated mice with the most commonly used anti-TB drugs -- isoniazid, rifampicin and pyrazinamide -- for a period of eight weeks.
The findings, published in the Mucosal Immunology journal, showed that while all three drugs significantly altered the composition of the mice's gut microbiome, only mice treated with isoniazid combined with pyrazinamide showed an increase in vulnerability to Mtb infection due to a compromised gut microbiota.
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The researchers transplanted faeces from mice that had been treated with anti-TB drugs (specifically isoniazid and pyrazinamide) into untreated mice prior to infection and showed that faecal transplant was sufficient to compromise immunity to Mtb.
Further, the team found that after the anti-TB treatment, alveolar macrophages -- a type of immune cell located in the airways of mice and humans -- were compromised in their ability to kill Mtb.
"We need to do more research in order to understand how the microbiome affects alveolar macrophages because these cells are critical for controlling early TB infection," King said.
"We also need to identify the molecular pathways involved in the gut-lung axis."
According to the World Health Organization, TB is one of the top 10 causes of death worldwide.
In 2017, 10 million people fell ill with TB, and 1.6 million died from the disease (including 0.3 million among people with HIV).
The infection also accounted for death in 230,000 children (including children with HIV associated TB) in 2017.
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